Dec 09 2016

Trouble for the FDA?

fdaThere is persistent tension over the issue of drug regulations. On one side are those who think that before we sell drugs to the public with health claims, we should ensure there is a reasonable amount of objective quality scientific evidence to demonstrate that the drugs are safe and effective. I admit this is the side of the discussion on which I fall, and it is clear that most of the public assumes this is the case.

The other perspective is that requiring too much research and regulation slows the passage of potentially new and lifesaving drugs to the public. Potentially useful drugs should be fast tracked as much as possible. In the extreme version, held by some Libertarians, there should be no regulation (or perhaps minimal regulation for safety) and the free market should sort out what works and what doesn’t.

The Food and Drug Administration (FDA) is the regulatory agency in the US responsible for ensuring the safety of drugs and that efficacy claims are backed by adequate evidence. The FDA, however, is a creature of congress, from which it derives its authority. It can only do what the law says it can do. Within that law the FDA also has a certain amount of discretion. How much evidence is enough is a judgment call. Therefore who heads the FDA can have a significant impact on how tightly or loosely regulated the pharmaceutical industry is at any given time.

The FDA’s mandate is now being threatened from both ends, congressional law and possible picks by Trump to head the FDA.

Congress has just passed the 21st Century Cures act, which is a terrible law that weakens FDA regulations and shifts the power tremendously in the direction of the pharmaceutical industry. Like most modern bills, this is a large and complex bill with many pieces. Some of those pieces are good, providing funding for research. The core of the bill, however, is based upon a false premise and provide a counterproductive fix.

Orac has already done a great job of summarizing the problems with the bill. He writes:

The FDA already has the tools to do what the 21st Century Cures Act demands without weakening patient protections or scientific rigor. In fact, the FDA, despite being underfunded, is actually remarkably efficient at new drug approvals, evaluating nearly all new drug applications within 6 to 10 months, an impressive turnaround for such complex assessments. It’s been pointed out that the FDA actually acts more rapidly than most European regulatory agencies. Basically, there is no evidence that the FDA hampers overall medical innovation, nor is there evidence that the FDA’s current requirements lead to higher drug prices or cost lives.

The justification for the bill is based upon an empirical claim, that the FDA is “too slow” and therefore delays effective drugs getting to market, costing lives. This claim is pure nonsense. There is always a balance between scientific rigor and timely efficiency, and over the decades this balance has been carefully calibrated at the FDA. It is already as close as you can get to optimal. If anything, in my opinion, it could use tweaks that would tighten regulations. This can be done without slowing the process.

The Cures Act throw out this carefully calibrated balance over the false fear that the FDA is restricting access to potentially useful drugs. Again, there are some good things in the bill, but the bad things are bad. The bill, for example, makes provisions for using weaker forms of evidence to approve drugs or expand drug indications:

  • the sources of real world evidence, including ongoing safety surveillance, observational studies, registries, claims, and patient-centered outcomes research activities;

There is also a provision specifically to weaken the evidence necessary for approval of stem cell treatments:

Creates an expedited review pathway for “regenerative medicine” products that allows use of surrogate endpoints and post-approval studies.

Meanwhile, scientific reviews have found that relying upon these types of weaker evidence leads to the premature adoption of treatments that do not work. So-called “real world” data is useful, but cannot be used to establish efficacy. This is crystal clear. Surrogate endpoints are also useful to guide research, but should not be used for efficacy claims. This means that instead of showing that patients actually get better, you can just show that their blood work looks better.

These trends are directly against what we are advocating at Science-Based Medicine (SBM). It’s difficult to review the hundreds of articles that have established our position over the years, but basically it is clear that relying on weaker forms of evidence leads to unreliable conclusions, premature adoption of worthless or even harmful treatments, and a tremendous amount of waste.

It’s important to remember that we (meaning health-care providers and the public) all want the same thing, even if we have different perspectives. We all want to maximize the pace of medical advance, to get the most effective treatments to patients as quickly as possible. There is also some room for reasonable disagreements about how to achieve this mutual goal.

What is important, however, is that when discussing how to achieve this goal we look at the relevant evidence that exists, and we carefully consider all sides of the issue. If you only see regulation as a burden, and you ignore the scientific evidence, you will end up with ineffective regulations that do not accomplish your goals. I think that is what is happening here.

In addition there are interests with other goals. The pharmaceutical industry has a massive conflict of interest with regard to this question. Their motivated reasoning is therefore equally massive. There are also ideologues who are simply anti-regulation, and their motivated reasoning is equally massive.

The other threat to the optimal effectiveness of the FDA comes from the president-elect. He is considering Jim O’Neill to head the FDA. O’Neill is a Libertarian who actually believes that the FDA should not require any evidence of efficacy before allowing a drug on the market. In 2014 he said:

“We should reform FDA so there is approving drugs after their sponsors have demonstrated safety—and let people start using them, at their own risk, but not much risk of safety. Let’s prove efficacy after they’ve been legalized.”

Yikes. Imagine this guy as head of the FDA. Of course, this is what we have with the supplement industry. We don’t have to speculate about what will happen, we know what will happen – a flood of useless products with misleading claims. The public will flush billions of dollars down the drain on products that don’t work, and risk their health relying on ineffective medical products. There is no question that is what will happen, because that is exactly what happened with supplements, and with homeopathy (which also do not require evidence of efficacy).

I am a fan of the free market and recognize its power to self-regulate and essentially process the information that comes from millions of individual buying decisions. There are some things you cannot regulate by committee. The libertarian fallacy, however, is to take that principle too far, and to treat the free market as a magic wand. It is powerful, but not infinitely powerful. This is because there are many subtle ways to distort the market, and the market does not always perceive or respond to the factors that we would want.

In the case of drugs, consumers are actually very poor at perceiving quality. This is demonstrably the case, there is no real debate about this. There are a few simple reasons for this. The first is that the effect of many drugs is statistical. Taking an aspirin a day can reduce your risk of heart attacks and strokes, but there is absolutely no way for an individual to know if taking an aspirin actually works. The only way to know is through carefully scientific research. The same is true for many drugs, there is simply no way for the consumer to know if they are working.

For drugs that have a more immediate effect, there is the placebo effect to contend with. Most symptoms patients will get are self-limiting, or have a natural variability, or are subjective. This can make any treatment seem to work.

Only treatments that have a dramatic and fairly rapid objective effect would be sorted out through such anecdotal evidence (and even then a lot of crap would slip through – again, witness the multi-billion dollar homeopathy industry). Companies could put any crap they want in a bottle, as long as it was not directly harmful, and make any claims they want for it, and people will buy it.

If O’Neill’s philosophy were enacted to any extent at the FDA, it would be a disaster for health consumers (i.e. everyone). Trump has not made the appointment yet, so there is still some hope. However, he has already appointed a global warming denier to the EPA, and other cabinet members to agencies whose core mission they oppose. Appointing O’Neill would be in line with some of his existing appointments, so it is unfortunately plausible.

The evidence is already clear – the best outcomes result from efficient and effective regulations requiring high quality evidence for safety and efficacy prior to marketing a drug or health product. This is also what the public expects. This common sense and evidence-based approach, however, is under constant attack by ideologues, industry interests, and simple wishful thinking. The latter may be the most dangerous, because it is bipartisan.

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